Fimbrolides (halogenated 5-methylene-2(5H)-furanones) possess a wide range of important biological properties including antifungal and antimicrobial properties (see WO 96/29392 and WO 99/53915, the disclosures of which are incorporated herein by cross-reference). These metabolites can be isolated from red marine algae Delisea fimbriata, Delisea elegans and Delisea pulchra. 
In spite of recently discovered biological significance of fimbrolides, there is not at present a general method suitable for the large-scale synthesis of these metabolites. The few reported syntheses of these metabolites utilise either the sulfuric acid-catalysed cyclisation of brominated levulinic acid at elevated temperatures (Tetrahedron 1997, 53: 15813-15826) or use (E)-β-bromo-β-lithioacrylate (J. Org. Chem. 1985, 50, 2195-2198) or allenes (J. Org. Chem. 1995, 60, 1814-1822) as starting materials.
Known acids used in the cyclisation reaction include 100% or 98% sulfuric acid which causes a high degree of charring during the reaction thus producing large quantities of intractable materials. Furthermore copious amounts of water are required to quench these reactions, a process that generates a large quantity of aqueous acidic waste.
These reactions are non-selective, extremely difficult to control and lead to mixtures of different products due to scrambling of bromines atoms under these conditions. Exhaustive chromatography is required to separate the reaction products and this results in low yields of desired 4-bromo-5-(bromomethylene)-, 5-(dibromomethylene)-, 4-bromo-5-(dibromomethylene)-2(5H)-furanones. The chromatography required is tedious and often impractical for large scale reactions.
The compounds 3-alkyl-4-bromo-5-(bromomethylene)- and 3-alkyl-5-(dibromomethylene)-2(5H)furanones are key intermediates in the synthesis of highly of active side chain functionalised furanones (see WO 99/54323, the disclosure of which is incorporated herein by cross-reference). Accordingly, there is a need for more efficient and reliable syntheses of parent furanones.
We have found conditions that, surprisingly, enable the cyclisation of halogenated 4-oxoalkanoic acids under mild conditions. We have found this discovery to be particularly useful in cyclising brominated 4-oxopentanoic acids under mild conditions to afford high yields of brominated 2(5H)furanones or tetrahydro-2(5H)-furanones under mild conditions. Furthermore tetrahydrofuranones generated under these conditions can be dehydrobrominated to yield a range of 5-(methylene)-, 5-(bromomethylene)-, 5-(dibromomethylene)- or 4-bromo-5-(bromomethylene)-2(5H)-furanones. These furanones can be further functionalised to yield novel analogues of Delisea metabolites.